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Allantoin/Azelaic Acid 1589

Amiloxate (USAN, rINN) 3. Hughes CG. Oral PABA and vitiligo. J Am Acad Dermatol 1983; Avobenzone (USAN, rINN)
9: 770.
Amiloxato; Amiloxatum; E-1000; Isoamyl p-Methoxycinnamate. 4. Worobec S, LaChine A. Dangers of orally administered para- Avobenzona; Avobenzonum; Butylmethoxydibenzoylmethane;
Isopentyl p-methoxycinnamate; 3-(4-Methoxyphenyl)-2-prope- aminobenzoic acid. JAMA 1984; 251: 2348. 4-tert-Butyl-4-methoxydibenzoylmethane. 1-(p-tert-Butylphe-
noic acid 3-methylbutyl ester. Pharmacokinetics nyl)-3-(p-methoxyphenyl)-1,3-propanedione; 1-[4-(1,1-dimeth-
If given orally, aminobenzoic acid is absorbed from the gastroin- ylethyl)phenyl]-3-(4-methoxyphenyl)-1,3-propanedione.
C 15 H 20O 3 = 248.3. testinal tract. It is metabolised in the liver and excreted in the
urine as unchanged drug and metabolites.
C AS 71617-10-2.
C 20 H 22 O 3 = 310.4.
Uses and Administration
Aminobenzoic acid is applied topically as a sunscreen (p.1576). C AS 70356-09-1.
O Aminobenzoic acid and its derivatives effectively absorb light
throughout the UVB range but absorb little or no UVA light (for
definitions, see p.1580). Aminobenzoate sunscreens may there- CH3
H3C O O fore be used to prevent sunburn, but are unlikely to prevent drug- H 3C
related or other photosensitivity reactions associated with UVA O
CH3 H 3C CH3
light; combination with a benzophenone may give some added
H 3C protection against such photosensitivity.
Aminobenzoic acid has sometimes been included as a member
NOTE. Neo-Heliopan E 1000 is a trade name that has been used of the vitamin-B group, but deficiency of aminobenzoic acid in
man or animals has not been found.
O O
for amiloxate.
Pharmacopoeias. In US. Aminobenzoic acid has been used with bentiromide (p.2264) in
the PABA or BTPABA test of pancreatic function. NOTE.Escalol 517, Eusolex 9020, Neo-Heliopan 357, and Parsol
USP 31 (Amiloxate). Store in airtight containers. 1789 are trade names that have been used for avobenzone.
Preparations
Profile Pharmacopoeias. In US.
USP 31: Aminobenzoic Acid Gel; Aminobenzoic Acid Topical Solution.
Amiloxate, a substituted cinnamate, is a sunscreen (p.1576) with USP 31 (Avobenzone). M.p. 81 to 86. Store in airtight con-
actions similar to those of octinoxate (p.1608). It is effective Proprietary Preparations some preparations are listed in Part 3.
tainers. Protect from light.
against UVB light (for definitions, see p.1580).
Preparations Profile
Ammonium Lactate (USAN) Avobenzone is a substituted dibenzoylmethane used by topical
Proprietary Preparations some preparations are listed in Part 3. application as a sunscreen (p.1576). Dibenzoylmethanes absorb
Amonio, lactato de; BMS-186091.
light in the UVA range (for definitions, see p.1580) and may
therefore be used with other sunscreens that absorb UVB light to
C 3 H 9 NO 3 = 107.1. prevent sunburn; they will also provide some protection against
Aminobenzoic Acid C AS 52003-58-4. drug-related or other photosensitivity reactions associated with
Acide 4-Aminobenzoque; Acidum 4-aminobenzoicum; Amben; ATC Vet QA16QA04. UVA light.
4-Aminobensoesyra; 4-Aminobentsoehappo; 4-aminobenzoe-
_ Contact and photocontact allergic dermatitis has occasionally
sav; Aminobenzoico, cido; 4-Aminobenzoine ru gtis; Kwas 4- been reported with the topical use of dibenzoylmethane sun-
aminobenzoesowy; Kyselina 4-aminobenzoov; PAB; PABA; Pa- O NH4+
screens.
bacidum; Para-aminobenzoic Acid; Vitamin Bx; Vitamin H. 4- O-
Aminobenzoic acid. Preparations
H3C
Proprietary Preparations numerous preparations are listed in
C 7 H 7 NO 2 = 137.1. OH Part 3.
C AS 150-13-0.
ATC D02BA01. Profile
ATC Vet QD02BA01. Ammonium lactate is a humectant applied as a cream or lotion
containing 12% lactic acid neutralised with ammonium hydrox- Azelaic Acid (USAN, rINN)
ide. It is used in the treatment of dry scaly conditions of the skin
O OH including ichthyosis. Adverse effects of topical ammonium lac- Acide azlaque; cido azelaico; Acidum azelaicum; Anchoic acid;
tate preparations include transient erythema, burning, and sting- Atselaiinihappo; Azelaik Asit; Azelainsyra; Lepargylic acid; ZK-
ing. Treated areas may be more sensitive to sunlight and expo- 62498. Nonanedioic acid; Heptane-1,7-dicarboxylic acid.
sure should be minimised.

Preparations
C 9 H 16 O 4 = 188.2.
Proprietary Preparations (details are given in Part 3)
Arg.: Lacto-Cev; Lactrex; Braz.: Lac-Hydrin; Canad.: Lac-Hydrin; Chile: C AS 123-99-9.
Kerapil; Topilact 12; Fr.: Kerapil; Malaysia: Lanate; Mex.: Lac-Hydrin;
NH2 NZ: Lac-Hydrin; Lanate; Singapore: Lac-Hydrin; Lanate; USA: Amlactin; ATC D10AX03.
Geri-Hydrolac; Kerasal AL; Lac-Hydrin; LAC-Lotion. ATC Vet QD10AX03.
Pharmacopoeias. In Eur. (see p.vii) and US. Multi-ingredient: Arg.: Clobeplus; Clobesol LA; Lactiderm; Lactiderm
Ph. Eur. 6.2 (4-Aminobenzoic Acid; Aminobenzoic Acid BP HC; Lacto-Cev Zn; Urecrem Hidro; Braz.: Lactrex; Chile: Ichtyosoft;
KPL; Lactrex; Queratopil; Fr.: I-Soft; Ichtyosoft; Keralac Plus; Zeniac
2008). White or slightly yellow crystalline powder. Slightly sol- LP Fort; Zeniac LP; Zeniac; Indon.: Exfoliac; Ital.: Alfa Acid; Ipso Urea; O O
uble in water; freely soluble in alcohol; it dissolves in dilute so- Mex.: Lactrex; Port.: Lactonico; Venez.: Lactrex.
lutions of alkali hydroxides. Protect from light.
USP 31 (Aminobenzoic Acid). White or slightly yellow, odour- HO OH
less crystals or crystalline powder. It discolours on exposure to
air or light. Slightly soluble in water and in chloroform; freely
Arbutin
soluble in alcohol and in solutions of alkali hydroxides or car- Arbutoside; Arbutyna; Beta-arbutin; Ursin. 4-Hydroxyphenyl-D- Adverse Effects and Precautions
bonates; sparingly soluble in ether. Store in airtight containers. glucopyranoside. Topical application of azelaic acid may produce a tran-
Protect from light. sient skin irritation such as burning, stinging, pruritus,
Adverse Effects and Precautions C 12 H 16 O 7 = 272.3.
C AS 497-76-7 (beta-arbutin); 84380-01-8 (alpha-ar- dryness, and scaling. It is usually mild and disappears
Adverse skin reactions such as local irritation and contact derma- on continued treatment, but in a few patients the irrita-
titis have been reported after the topical use of aminobenzoate butin).
sunscreens. Aminobenzoate sunscreens should not be used by tion may persist, requiring reduced frequency of appli-
those with a history of photosensitivity or hypersensitivity reac- cation or temporary suspension of treatment. There
tions to structurally related drugs such as sulfonamides, thiazide HO have been rare reports of hypopigmentation, rash, and
diuretics, and ester-type local anaesthetics. photosensitivity. Azelaic acid should not be applied to
Aminobenzoic acid may stain clothing. O OH
O the eyes, mouth, or other mucous membranes.
Allergic and photoallergic contact dermatitis have been report- OH
ed after topical use of aminobenzoic acid or its esters.1 Early re- Uses and Administration
OH
ports of such reactions led to the removal of these compounds
from sunscreen preparations (many are now described as PA- OH Azelaic acid inhibits the growth of Propionibacterium
BA-free), although padimate O still appears to be widely used.2 spp. and reduces keratinisation. It is used in the topical
Patients allergic to aminobenzoic acid may also react to structur- Profile treatment of mild to moderate inflammatory acne
ally related allergens such as para-aminobenzoic acid ester an- Arbutin is a glycosylated derivative of hydroquinone (p.1598) (p.1577) and for the inflammatory papules and pus-
aesthetics, sulfonamides, and paraphenylenediamine in hair extracted from bearberry (p.2263) and similar plants. It is used
tules of mild to moderate rosacea (p.1583). It has also
dyes.1,2 topically in concentrations of 1 to 5% as a depigmenting agent
for the skin in hyperpigmentation disorders. The higher concen- been tried in hyperpigmentary skin disorders such as
Skin reactions (vitiligo) have also been reported with oral ami-
nobenzoic acid3 and the adverse effects associated with the trations may lead to a paradoxical hyperpigmentation. melasma, and in malignant melanoma.
former use of high oral doses for various conditions have been Alpha-arbutin has been used similarly. In the treatment of acne azelaic acid is applied twice
highlighted.4 Preparations daily for up to 6 months as a 20% cream or 15% gel.
1. Scheuer E, Warshaw E. Sunscreen allergy: A review of epidemi- Proprietary Preparations (details are given in Part 3)
ology, clinical characteristics, and responsible allergens. Derma- Improvement usually occurs within four weeks.
titis 2006; 17: 311. Correction. ibid.; 162. Multi-ingredient: Arg.: Cellskinlab Phyto Spot; Melasoft; Chile: Phyto
2. Mackie BS, Mackie LE. The PABA story. Australas J Dermatol
Corrective Gel; Phyto Spot; Port.: Despigmentante. For the treatment of mild to moderate rosacea, a 15%
1999; 40: 513. gel should be applied to the affected area twice daily
The symbol denotes a preparation no longer actively marketed The symbol denotes a substance whose use may be restricted in certain sports (see p.vii)
1590 Dermatological Drugs and Sunscreens
for a period of up to 12 weeks. Improvement usually Preparations that has a device for the release of excess pressure. Unused ma-
occurs in 4 to 8 weeks. Proprietary Preparations (details are given in Part 3) terial should not be returned to its original container but should
Austria: Regranex; Canad.: Regranex; Cz.: Regranex; Fr.: Regranex; Ger.: be destroyed by the addition of sodium hydroxide solution
References. Regranex; Gr.: Regranex; Israel: Regranex; Mex.: Regranex; Neth.: Re- (10%). Destruction can be considered to be complete if the addi-
granex; Port.: Regranex; Spain: Regranex; Switz.: Regranex; UK: Regran- tion of a crystal of potassium iodide does not result in the release
1. Fitton A, Goa KL. Azelaic acid: a review of its pharmacological ex; USA: Regranex.
properties and therapeutic efficacy in acne and hyperpigmentary of free iodine after acidification with dilute hydrochloric acid.
skin disorders. Drugs 1991; 41: 78098. Multi-ingredient: USA: GEM 21S. Protect from light.
2. Breathnach AS. Melanin hyperpigmentation of skin: melasma, USP 31 (Hydrous Benzoyl Peroxide). It contains not less than
topical treatment with azelaic acid, and other therapies. Cutis 65% and not more than 82% of anhydrous benzoyl peroxide with
1996; 57 (suppl): 3645.
Bemotrizinol (USAN, rINN) a water content of about 26%. The hydrous form is a white gran-
3. Elewski B, Thiboutot D. A clinical overview of azelaic acid.
Cutis 2006; 77 (suppl): 1216. Bmotrizinol; Bemotrizinolum; BEMT; Bis-ethylhexyloxyphenol ular powder with a characteristic odour. Sparingly soluble in wa-
4. Del Rosso JQ. The use of topical azelaic acid for common skin
ter and in alcohol; soluble in acetone, in chloroform, and in ether.
Methoxyphenol Triazine; FAT-70884. 2,2-[6-(4-Methoxyphe-
disorders other than inflammatory rosacea. Cutis 2006; 77 (sup- Store in the original container, treated to reduce static charges.
nyl)-1,3,5-triazine-2,4-diyl]bis{5-[(2-ethylhexyl)oxy]phenol}. Unused material should not be returned to its original container
pl): 224.
5. Liu RH, et al. Azelaic acid in the treatment of papulopustular but should be destroyed by the addition of sodium hydroxide so-
rosacea: a systematic review of randomized controlled trials. C 38 H 49N 3 O 5 = 627.8. lution (10%). Destruction can be considered to be complete if the
Arch Dermatol 2006; 142: 104752. C AS 187393-00-6. addition of a crystal of potassium iodide does not result in the re-
Preparations lease of free iodine.
Proprietary Preparations (details are given in Part 3) OCH

Arg.: Cutacelan; Austral.: Finacea; Skinoren; Austria: Skinoren; Belg.: Ski-


Adverse Effects and Precautions
noren; Braz.: Azelan; Dermizan; Cz.: Aknoren; Skinoren; Denm.: Finacea; Topical application of benzoyl peroxide may produce
Skinoren; Fin.: Skinoren; Fr.: Finacea; Skinoren; Ger.: Skinoren; Gr.: Alen- skin irritation, particularly at the start of treatment. In
zantyl; Azedose; Azelac; Azelaxine; Azelderm; Cevigen; Chemilaic; Exazen;
Forcilen; Kenedril; Noreskin; Opilet; Prevolac; Skinoren; Sonalent; OH N N OH some patients the irritation may require reduced fre-
Zelicrema; Zorkenil; Zumilin; Hong Kong: Qualicren; Qualilaic; Skinoren; quency of application or temporary suspension of
Hung.: Skinoren; Indon.: Aza 20; Skinoren; Zelface; Zeliris; Irl.: Skinoren; N
Israel: Skinoderm; Ital.: Acnezaic; Finacea; Neocutis; Skinoren; Malay- treatment. Skin dryness, peeling, rash, and transient lo-
sia: Skinoren; Mex.: Cutacelan; Finacea; Norw.: Finacea; Skinoren; NZ: H C O O CH
cal oedema may also occur. Contact sensitisation has
Skinoren; Philipp.: Skinoren; Pol.: Acne-Derm; Hascoderm; Skinoren;
Port.: Dermazil; Finacea; Skinoren; Rus.: Skinoren (); S.Afr.: Ski- H C CH been reported in some patients using preparations con-
noren; Singapore: Skinoren; Spain: Finacea; Skinoren; Zeliderm; Swed.: taining benzoyl peroxide. Caution is required when ap-
Finacea; Skinoren; Switz.: Skinoren; Thai.: Skinoren; Turk.: Azelderm; Ski- NOTE. Tinosorb S is a trade name that has been used for bemot-
noren; UK: Finacea; Skinoren; USA: Azelex; Finacea; Finevin; Venez.: Cuta- plying it near the eyes, the mouth and other mucous
celan. rizinol.
membranes, and to the neck and other sensitive areas.
Multi-ingredient: Austral.: Acnederm Medicated; Hong Kong: Acned- Profile Patients should be alerted to benzoyl peroxides
erm; Ital.: Zeroac; Malaysia: Acnederm Lotion; NZ: Acnederm; Singa- Bemotrizinol is used as a sunscreen (p.1576). It is effective
pore: Acnederm. against UVA light (for definitions, see p.1580). bleaching property.
Preparations Body odour. An unusual unpleasant body odour in a patient
Proprietary Preparations some preparations are listed in Part 3. was attributed to the topical use of benzoyl peroxide.1
Becaplermin (BAN, USAN, rINN) 1. Molberg P. Body odor from topical benzoyl peroxide. N Engl J
Med 1981; 304: 1366.
Becaplermina; Bcaplermine; Becaplerminum; Bekaplermiini;
Carcinogenicity. There has been concern at the implications of
Bekaplermin; RWJ-60235. Recombinant human platelet-derived Bentoquatam (USAN) some animal studies showing benzoyl peroxide to possess some
growth factor B. Quaternium 18-bentonite. tumour-promoting activity.1 However, a retrospective survey in
Canada concluded that there was no indication that the normal
C AS 165101-51-9. C AS 1340-69-8. use of benzoyl peroxide in the treatment of acne was associated
ATC D03AX06. with an increased risk of facial cancer.2 A comprehensive
Profile review3 that included in-vitro and animal studies, as well as hu-
ATC Vet QD03AX06. Bentoquatam, described as an organoclay compound, is a barrier man data, also concluded that there was no evidence to associate
Profile preparation that is applied topically as a 5% lotion to prevent al- the topical use of benzoyl peroxide with the development of skin
Becaplermin is a recombinant human platelet-derived growth lergic contact dermatitis caused by poison ivy, poison oak, or cancer in humans. However, the International Agency for Re-
factor (rhPDGF-BB) that enhances the formation of granulation poison sumac. The lotion is applied in a sufficient quantity to search on Cancer4 considers that there is inadequate evidence in
tissue and promotes wound healing (p.1585). Becaplermin is ap- form a visible coating 15 minutes before possible contact with humans and its overall evaluation is that benzoyl peroxide is not
plied topically as a 0.01% gel in the management of full thick- the plants. If continued protection is required the lotion may be classifiable as to its carcinogenicity to humans.
ness neuropathic diabetic skin ulcers (see Diabetic Complica- re-applied every 4 hours or at any time if the visible coating is
1. Jones GRN. Skin cancer: risk to individuals using the tumour
tions, p.433). It is applied once daily, covered by a moist saline removed. promoter benzoyl peroxide for acne treatment. Hum Toxicol
gauze dressing, for up to 20 weeks. If no meaningful healing Preparations 1985; 4: 758.
process (decrease in ulcer size of about 30%) is evident after 10 2. Hogan DJ, et al. A study of acne treatments as risk factors for
Proprietary Preparations (details are given in Part 3) skin cancer of the head and neck. Br J Dermatol 1991; 125:
weeks of therapy, treatment should be re-assessed. USA: Ivy Block. 3438.
Becaplermin should not be applied to ulcers where neoplasms 3. Kraus AL, et al. Benzoyl peroxide: an integrated human safety
are present or to clinically infected ulcers. If the ulcer becomes assessment for carcinogenicity. Regul Toxicol Pharmacol 1995;
infected during therapy, becaplermin should be stopped until the 21: 87107.
infection has cleared. US licensed product information warns Benzoyl Peroxide (USAN) 4. IARC/WHO. Benzoyl peroxide. IARC monographs on the eval-
uation of carcinogenic risks to humans volume 71 1999. Availa-
that an increased rate of death from all cancers has been seen in Bensoylperoxid; Bentsoyyliperoksidi; Benzoilo peroksidas; Ben- ble at: http://monographs.iarc.fr/ENG/Monographs/vol71/
patients treated with 3 or more tubes of becaplermin gel (tube zoil-peroxid; Benzoyil Peroksit; Benzoylis peroxidum; Benzoylper- volume71.pdf (accessed 27/09/07)
size not specified).
oxid; NSC-675; Perxido de benzoilo; Peroxyde de benzoyle. Handling. Benzoyl peroxide powder may explode if subjected
Becaplermin is used with a resorbable synthetic calcium phos- Dibenzoyl peroxide. to grinding, percussion, or heat. Hydrous benzoyl peroxide con-
phate matrix to promote bone and tissue growth in the treatment taining water to reduce the risk of explosion may still explode if
of periodontal disease. It is also under investigation in the treat- ;
C 14 H 10O 4 = 242.2. exposed to temperatures higher than 60 or cause fires in the
ment of osteonecrosis of the jaw, fractures, and osteoporosis, and presence of reducing substances.
in the repair of cartilage, ligament, and tendon injuries. C AS 94-36-0 (anhydrous benzoyl peroxide).
ATC D10AE01. Hypersensitivity. Benzoyl peroxide appears to induce contact
References. hypersensitivity quite often when used to treat leg ulcers,1 but it
ATC Vet QD10AE01; QD11AX90.
1. Wieman TJ, et al. Efficacy and safety of a topical gel formulation is unclear how often this occurs when used in the treatment of
of recombinant human platelet-derived growth factor-BB (beca- acne.2 Patch testing3,4 in some studies suggests that up to 76% of
plermin) in patients with chronic neuropathic diabetic ulcers: a patients may be hypersensitive to benzoyl peroxide but this does
phase III randomized placebo-controlled double-blind study. Di- O
abetes Care 1998; 21: 8227. not appear to correlate either with the clinical irritation produced
2. Smiell JM, et al. Efficacy and safety of becaplermin (recom- O O during treatment, which usually resolves on continued use, or
binant human platelet-derived growth factor-BB) in patients with the reported incidence of hypersensitivity.2,4 In one study
O 25% of patients were considered to be hypersensitive from patch
with nonhealing, lower extremity diabetic ulcers: a combined
analysis of four randomized studies. Wound Repair Regen 1999; testing but only 2 of 44 patients developed clinical hypersensitiv-
7: 33546. ity.4 Another study involving 204 patients with acne found that
3. Guzman-Gardearzabal E, et al. Treatment of chronic ulcers in the incidence of false-positive irritant skin reactions to benzoyl
the lower extremities with topical becaplermin gel .01%: a mul- peroxide was about 15% but only 1% of the patients had true
ticenter open-label study. Adv Therapy 2000; 17: 1849.
allergic reactions to the drug on further testing.5 However, there
4. Mandracchia VJ, et al. The use of becaplermin (rhPDGF-BB) gel (anhydrous benzoyl peroxide) has been concern that hypersensitivity to benzoyl peroxide may
for chronic nonhealing ulcers: a retrospective analysis. Clin Po-
diatr Med Surg 2001; 18: 189209. be mistaken for irritation or worsening of the acne.3
5. Nagai MK, Embil JM. Becaplermin: recombinant platelet de- Pharmacopoeias. In Chin., Eur. (see p.vii), Int., and US. 1. Vena GA, et al. Contact dermatitis to benzoyl peroxide. Contact
rived growth factor, a new treatment for healing diabetic foot Ph. Eur. 6.2 (Benzoyl Peroxide, Hydrous). It contains not less Dermatitis 1982; 8: 338.
ulcers. Expert Opin Biol Ther 2002; 2: 21118. than 70% and not more than 77% of anhydrous benzoyl peroxide 2. Cunliffe WJ, Burke B. Benzoyl peroxide: lack of sensitization.
6. Nevins M, et al. Platelet-derived growth factor stimulates bone and not less than 20% of water. It rapidly loses water on exposure Acta Derm Venereol (Stockh) 1982; 62: 4589.
fill and rate of attachment level gain: results of a large multicent- to air and may explode if the water content is too low. A white or 3. Leyden JJ, Kligman AM. Contact sensitization to benzoyl perox-
er randomized controlled trial. J Periodontol 2005; 76: 220515. ide. Contact Dermatitis 1977; 3: 2735.
almost white, amorphous or granular powder. Practically insolu- 4. Rietschel RL, Duncan SH. Benzoyl peroxide reactions in an acne
7. McGuire MK, et al. rhPDGF-BB promotes healing of periodon-
tal defects: 24-month clinical and radiographic observations. Int ble in water; slightly soluble in alcohol; soluble in acetone; solu- study group. Contact Dermatitis 1982; 8: 3236.
J Periodontics Restorative Dent 2006; 26: 22331. Correction. ble in dichloromethane with separation of water. Store at 2 to 8 5. Balato N, et al. Acne and allergic contact dermatitis. Contact
ibid. 2007; 27: 88. in a container that has been treated to reduce static charges and Dermatitis 1996; 34: 689.

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